"Stress" is known to be a contributing factor in the development of psychopathology, and thus is of interest from a mental health perspective. Brain noradrenergic (NE) and serotonergic (5HT) neurons have been implicated strongly in the adaptive behavioral and physiological response of mammalian organisms to various behavioral/environmental and physiological/internal challenges. This involvement appears to be bidirectional in that these neurons facilitate the global organismic response to these challenges and, in turn, are influenced by them. The present experiments seek to extend this line of investigation to a more precise degree by examining these relationships at the single unit level. Our approach is unique in that the activity of brain NE and 5HT neurons will be studied in behaving animals, and, in addition, in conjunction with various peripheral physiological indices. A series of experiments employing behavioral or physiological challenges are proposed, with the following aims. 1) An integration of behavioral and peripheral physiological studies of NE and 5HT neurons. 2) A comparison of the response of NE and 5HT neurons. 3) Relating changes in NE and 5HT unit activity to activation of the pituitary-adrenal vs. sympathetic nervous system. 4) A direct analysis of the relationship of changes in NE and 5HT unit activity to changes in the cardiovascular system. 5) A comparison of the effect of internal (visceral) and external (somatic) challenges. 6) A comparison of the importance of behavioral arousal and physiological challenge. 7) A comparison of arousal and noxious arousal. 8) Involvement of endogenous opioids in the response of 5HT and NE neurons to various challenges. 9) How changes in NE and 5HT unit activity are manifested functionally (masseteric reflex). These studies are of direct relevance to the N.I.M.H. because of the involvement of brain NE and 5HT neurons in arousal and emotionality, and more generally, because of the role of stress in the etiology of various forms of psychopathology.